L. A. S. van Kerkhoven1,2 L. G. M. van Rossum1 M. G. H. van Oijen1 A. C. I. T. L. Tan2 R. J. F. Laheij1 J. B. M. J. Jansen1
Upper gastrointestinal endoscopy does not reassure patients with functional dyspepsia
upper gastrointestinal endoscopy. Neither the anxiety nor the depression frequencies differed significantly before and after en− doscopy, either in patients with organic abnormalities at endos− copy or in those without. The general impression of health did not change after endoscopy either: organic abnormalities 62.7 27.4 vs. 64.9 24.2, P = 0.28; functional dyspepsia 61.0 27.9 vs. 62.8 27.2, P = 0.39. Only patients who had organic abnormalities reported a slightly improved quality of life 1 month after endoscopy: 0.74 0.15 vs. 0.78 0.12, P < 0.01. Conclusion: In patients with functional dyspepsia, upper gastro− intestinal endoscopy does not improve psychological well−being or health−related quality of life. In view of the invasiveness, cost, and potential harm associated with endoscopy, careful consid− eration should be given to whether this procedure should be car− ried out merely for the sake of the patient’s “peace of mind”.
Introduction
pathology in the proximal gut, thereby providing reassurance to the physician and, in particular, to the patient [4].
Functional dyspepsia ± defined as the presence of persistent up− per gastrointestinal symptoms without evidence of an organic disease that is likely to explain the symptoms ± continues to be an important clinical problem. In general, treatment is aimed at inhibiting gastric acid, but in most patients this is insufficient and symptoms persist [1 ± 3]. In these patients, upper gastroin− testinal endoscopy is often carried out in order to exclude serious
Extensive research has been conducted on the psychological as− pects of functional gastrointestinal diseases. In a study by Quadri and Vakil, it was shown that health−related anxiety declines after open−access endoscopy in patients who have high to moderate anxiety at the baseline [5]. Other studies have found that pa− tients with functional dyspepsia are more anxious and depressed
Institution Dept. of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands 2 Dept. of Gastroenterology and Hepatology, Canisius−Wilhelmina Hospital, Nijmegen, The Netherlands 1
Corresponding author L. van Kerkhoven, M. D. ´ Dept. of Gastroenterology and Hepatology ´ Radboud University Nijmegen Medical Center ´ PO Box 9101 ´ 6500 HB Nijmegen ´ The Netherlands ´ Fax: +31−243540103 ´ E−mail:
[email protected] Submitted 29 January 2006 ´ Accepted after revision 11 June 2006 Bibliography Endoscopy 2006; 38 (9): 879±885 Georg Thieme Verlag KG Stuttgart ´ New York ´ DOI 10.1055/s−2006−944661 ´ ISSN 0013−726X
Original article
Background and study aims: Upper gastrointestinal endoscopy in patients with functional dyspepsia is often carried out merely to reassure patients that symptoms are not due to serious pathology. The aim of this study was to compare anxiety, depres− sion, and health−related quality of life as proxy values for reas− surance in patients with functional dyspepsia before and after upper gastrointestinal endoscopy. Patients and methods: Consecutive patients referred for endos− copy between February 2002 and February 2004 were included in the study. They were asked to score anxiety and depression using the Hospital Anxiety and Depression Scale, health−related quality of life using the EuroQol−5D questionnaire, and their im− pression of their own general health using a visual analogue scale, 2 weeks before endoscopy and again 1 month afterwards. Results: A total of 420 patients were included, 42 % of whom were found to have an organic abnormality of some sort during
879
in comparison with healthy control individuals or patients in whom the symptoms have an organic cause [6 ± 11], and that the health−related quality of life (HRQL) is impaired in patients with functional dyspepsia in comparison with healthy control in− dividuals and patients with other chronic disorders such as asth− ma [12 ± 15].
Original article
By contrast, we demonstrated in a recent study that there is no difference in the level of anxiety or depression between patients with and without an organic cause of their symptoms before gas− trointestinal endoscopy [16]. Attempts have been made to quan− tify the effect of a negative endoscopy on HRQL [17], and a few studies have concluded that psychological well−being and HRQL improve along with the improvement of symptoms [12,18]. On the basis of these results, it was concluded that psychological distress develops as a result of the disorder, rather than causing the symptoms itself. Taking this into account, the policy of carry− ing out upper gastrointestinal endoscopy in order to reassure the patient appears illogical, since the diagnostic procedure is not likely to resolve the symptoms and will therefore not contribute to the patient’s psychological well−being. The objective of the present study was to investigate whether there are any differences in the level of psychological distress and in the HRQL, as proxy values for reassurance, before and after upper gastrointestinal endoscopy, between patients with and without an organic abnormality underlying the symptoms.
Patients and methods
880
nia, USA). All aspects of the protocol were approved by the med− ical ethics committees of Radboud University Nijmegen Medical Center and the Canisius−Wilhelmina Hospital, both in Nijmegen in the Netherlands. Anxiety and depression Anxiety and depression were measured using the Hospital Anxi− ety and Depression Scale (HADS). This is a self−completed ques− tionnaire that has been validated and can be used in a variety of clinical settings [19 ± 21]. It consists of 14 items and is divided into an anxiety subscale and a depression subscale, each consist− ing of seven questions rated on a scale ranging from 0 to 3, depend− ing on the severity of the problem described in the question. This allows utilities to be calculated that indicate the individual’s de− gree of anxiety or depression. A subscale score below 8 is consid− ered normal ± i. e., showing no signs of anxiety or depression [22]. Patients were defined as having mild to severe anxiety or depres− sion if they scored 8 or more on one of the respective subscales, al− though clinical signs might have been absent. Questions that were not filled out properly were not used for further analysis. Health−related quality of life The patients’ HRQL was assessed using the EuroQol−5D (EQ−5D) questionnaire, and their general impression of their own health in the previous weeks was assessed using a 100−mm visual ana− logue scale (VAS). The EQ−5D is a widely used multiple−attribute system suitable for assessing states of health. The EQ−5D classifi− cation describes health status in relation to five domains: mobi− lity, self−care, daily activities, pain/discomfort, and anxiety/de− pression at three levels, with 1 representing no dysfunction at all and 3 representing severe dysfunction. The validity and relia− bility of the questionnaire have been tested in a wide range of pa− tient groups [23, 24]. The VAS is a line with a standard length, with the extremes of the responses at each end. The scale ranges from 0 to 100, with 0 being the worst imaginable HRQL and 100 being the best. The patient is asked to mark the line at an appro− priate point, and the score is then obtained by measuring the dis− tance from the beginning of the line to that point.
Patients Between February 2002 and February 2004, consecutive patients referred for the first time for upper gastrointestinal endoscopy to the Canisius−Wilhelmina Hospital in Nijmegen, the Netherlands, were included. The institution is a general secondary−care dis− trict hospital. All of the patients were referred in accordance with the relevant guidelines in the Netherlands for general prac− titioners regarding the management of patients with dyspepsia. The guidelines state that an endoscopy is indicated if alarm symptoms are present, when the general practitioner needs reas− surance that there is no serious pathology underlying the symp− toms, or if symptoms recur or persist after empirical treatment with a proton−pump inhibitor (PPI) and Helicobacter pylori eradi− cation treatment.
Symptom score Patients were asked to complete a questionnaire including 32 items concerning gastrointestinal symptoms. The severity of the symptoms during the previous 4 weeks was rated on a 7−point Likert scale (with 0 meaning “absent” and 6 “very severe”). A score of two or more was regarded as symptom presence.
It was not feasible to exclude in advance any patients who had already undergone endoscopy during the previous 6 months. All patients referred for upper gastrointestinal endoscopy were therefore sent a questionnaire 2 weeks in advance of their ap− pointments. The patients were informed that they should return the questionnaire only if they had not had a previous upper gas− trointestinal endoscopy in the previous 6 months. The question− naire included enquiries regarding demographic data, the pres− ence and severity of gastrointestinal symptoms, anxiety and de− pression, and health−related quality of life (HRQL). The question− naire was repeated 1 month after the endoscopy, except for the questions concerning demographic data. All of the question− naires were processed using the Teleform automatic scanning program, version 6.0 (Cardiff Software, Inc., Sunnyvale, Califor−
Endoscopy The patients underwent routine diagnostic upper gastrointesti− nal endoscopy, and the outcomes were entered into a database. If necessary, histological data were obtained from biopsies taken during the endoscopy. The biopsies were analyzed by an experi− enced pathologist, and the results were entered into the same database. The results were retrieved from the database, and pa− tients were divided into groups according to their most promi− nent endoscopic outcome: carcinoma, gastric or duodenal ulcer, reflux esophagitis, other (e. g., esophageal varices, hiatal hernia, or fungus), and no organic abnormality underlying the symp− toms. When no endoscopic or histological explanation for the symptoms was found, the patients were defined as having func− tional dyspepsia.
Van Kerkhoven LAS et al. Endoscopy and reassurance in functional dyspepsia ´ Endoscopy 2006; 38: 879 ± 885
Table 1
Demographic data for the study group (n = 420) Functional dyspepsia (n = 245) n %
Male
Organic abnormalities (n = 175) n %
P
104
42
93
53
< 0.05
Previous endoscopy 1
89
36
73
42
0.26
Current smoking
34
14
31
18
0.28
Alcohol use 2
49
20
55
31
< 0.05
Coffee consumption 3
101
41
77
44
0.57
Dutch nationality
219
90
162
94
Mean age ( SD)
53 15
57 14
0.16 0.01
Either upper gastrointestinal endoscopy, lower gastrointestinal endoscopy, or sigmoidoscopy. The median consumption was 7 units/week. The numbers shown are for patients consuming more than 7 units/week. 3 The median consumption was 20 units/week. The percentages shown are for patients consuming more than 20 units/week. 2
Afterwards, the patients were informed of the outcome of the en− doscopy. If there was an organic abnormality, appropriate treat− ment was started; when there was no organic abnormality, the patients were reassured that there was no severe pathology un− derlying their symptoms. Statistical analyses Statistical analysis was carried out using the SAS statistics pro− gram, version 8.0 (SAS Institute, Inc., Minneapolis, Minnesota, USA). Data at baseline were analyzed using frequency tables and descriptive statistics. Patients with incomplete data were ex− cluded from further analysis. A paired t test was used to assess within−subject differences in the mean scores for anxiety, de− pression, HRQL, and the number of symptoms before and after endoscopy. The difference in the severity of symptoms was as− sessed using Wilcoxon’s signed−rank test. The influence of other variables on differences before and after endoscopy was assessed using linear regression models. Pearson’s chi−squared test was used to assess differences in the variables listed in Table 1. Pa− tients with coffee and alcohol consumption were divided into two groups depending on the median number of units consumed per week (20 and 7, respectively). A P value of < 0.05 was consid− ered statistically significant. Correlations between the total HADS scores, symptom severity, and the number of symptoms were calculated using Spearman’s rank correlation.
Results A total of 1769 questionnaires were sent and 932 were returned, 280 of which had to be excluded, as investigation of medical re− cords showed that the patients had undergone an upper gastro− intestinal endoscopy during the previous 6 months. The remain− ing 652 patients received the same questionnaire 1 month after endoscopy, and 515 of these questionnaires were returned. Nine− ty−five responders had to be excluded due to incomplete ques− tionnaires. Complete responses were available for 420 of the ini− tial 652 patients (64.4 %; 197 men, 223 women; mean age 55 15 years). A total of 175 patients were found to have an organic abnormali− ty at endoscopy: 2 % had carcinoma, 7 % had gastric ulcers, 5 % had duodenal ulcers, 55 % had reflux esophagitis, and 31 % had
another disorder (e. g., fungus, hiatal hernia). The patients with organic abnormalities were statistically significantly older, more often male, and consumed more alcohol in comparison with patients without an organic abnormality (Table 1). A pre− vious diagnostic intervention for upper gastrointestinal symp− toms, other than endoscopy (i. e., radiography, H. pylori testing), was reported by 39 % of the overall group of patients, and the pre− vious interventions were equally distributed among patients with and without an organic disorder at endoscopy (organic dis− order vs. functional dyspepsia: 37 % vs. 31 % for radiography, P = 0.19 and 12 % vs. 11 % for H. pylori, P = 0.76). Patients who re− ported having undergone a previous endoscopy (> 6 months be− fore the index endoscopy) were neither more anxious nor more depressed at baseline than patients who did not (OR 1.0; 95 % CI, 0.6 ± 1.5; and OR 1.3; 95 % CI, 0.8 ± 2.0, respectively). None of the variables listed in Table 1 were associated with a higher risk of anxiety, depression, or reduced HRQL. When the mean scores on the Hospital Anxiety and Depression Scale (HADS) before and after endoscopy were compared, only patients with an organic abnormality at endoscopy were found to show an improvement in anxiety scores (Table 2). Using the cut−off point of a score of 8 or more per subscale, 31 % of the pa− tients with an organic abnormality were anxious at baseline, in comparison with 28 % after endoscopy (P = 0.56), while 35 % of the patients with functional dyspepsia were anxious at baseline in comparison with 31 % after endoscopy (P = 0.33). Depression was present in 27 % of the patients in both groups, both before and after endoscopy. The general impression of health measured with the visual ana− logue scale did not improve over time in either group, nor were there any differences between the two groups before and after endoscopy. Patients with an organic abnormality at endoscopy reported a slight increase in the HRQL after endoscopy: mean 0.74 0.15 at T0 vs. 0.78 0.12 at T1 (P < 0.01). Both groups of pa− tients, with and without an organic abnormality, reported a sta− tistically significant improvement in symptom severity scores and a reduction in the mean number of symptoms (Table 2). Lin− ear regression analysis showed that none of the differences found in the outcomes listed in Table 2 were influenced by sex, age, alcohol consumption, or the presence of an organic disorder (Table 3).
Van Kerkhoven LAS et al. Endoscopy and reassurance in functional dyspepsia ´ Endoscopy 2006; 38: 879 ± 885
Original article
1
881
Table 2
Anxiety, depression, impression of general health, and quality of life before (T0) and after (T1) upper gastrointestinal endoscopy: subdivision in organic and functional dyspepsia
Original article
Anxiety Organic abnormalities Functional dyspepsia Depression Organic abnormalities Functional dyspepsia VAS Organic abnormalities Functional dyspepsia HRQL Organic abnormalities Functional dyspepsia Number of symptoms Organic abnormalities Functional dyspepsia Severity of symptoms Organic abnormalities Functional dyspepsia
n
T0 Mean SD
T1 Mean SD
Mean difference (95 % CI)
P
169 228
5.8 3.8 6.3 4.4
5.3 4.0 6.2 4.4
0.57 (0.15 to 0.99) 0.21 (±0.18 to 0.61)
< 0.01 0.28
169 236
5.1 3.7 5.3 4.3
4.9 4.1 5.3 4.5
0.21 (±0.17 to 0.60) ± 0.03 (±0.40 to 0.34)
0.28 0.87
175 245
62.7 27.4 61.0 27.9
64.9 24.2 62.8 27.2
± 2.16 (±6.06 to 1.74) ± 1.73 (±5.70 to 2.22)
0.28 0.39
177 236
0.74 0.15 0.72 0.17
0.78 0.12 0.72 0.18
± 0.04 (±0.05 to ±0.02) 0.00 (±0.02 to 0.02)
< 0.01 0.80
175 244
9.4 6.2 9.7 6.5
8.0 6.4 8.8 6.8
1.33 (0.72 to 1.93) 0.86 (0.30 to 1.42)
< 0.01 < 0.01
175 244
68.9 52.7 76.5 63.1
57.2 49.6 60.7 53.1
11.64 (3.79 to 19.49) 15.77 (7.87 to 23.66)
< 0.01 < 0.01
T0, 2 weeks before endoscopy; T1, 1 month after endoscopy; VAS, visual analogue scale measuring health−related quality of life in the previous week; HRQL, health−related quality of life.
Table 3
Multivariate linear regression analysis of the influence of various variables on the differences of outcome variables between T0 and T1 Anxiety b
Organic abnormality
882
0.35
R2 0.00
Depression b R2 0.24
0.00
VAS b 1.39
R2
HRQL b
R2
0.00
± 0.04
0.02
No. of symptoms b R2 0.46
Symptom severity b R2
0.00
± 4.13
0.00 0.01
Sex
0.04
0.00
± 0.28
0.00
± 0.35
0.00
0.00
0.00
± 0.01
0.00
± 9.50
Age
± 0.02
0.02
± 0.02
0.01
± 0.11
0.01
0.00
0.00
± 0.01
0.00
0.07
0.00
0.50
0.00
0.60
0.01
2.37
0.01
± 0.04
0.02
± 0.14
0.00
7.05
0.00
Alcohol usage Complete model
0.03
0.03
0.02
0.04
0.01
0.01
b, regression coefficient, representing the amount the dependent variable variable changes when the corresponding independent changes by one unit; R2, the total variance in the model explained by a specific variable. T0, 2 weeks before endoscopy; T1, 1 month after endoscopy; VAS, visual analogue scale measuring health−related quality of life in the past week; HRQL, health−related quality of life.
Finally, an increase in the total number of symptoms (Figure 1) was associated with an increase in mean scores on the HADS (correlation coefficient r = 0.78; P < 0.05). Figure 2 shows that when the total numbers of reported symptoms were divided into subgroups, the proportion of patients reporting mild to se− vere anxiety and depression also increased with an increasing number of symptoms. However, an increase in the severity of symptoms (Figure 3) was not associated with an increase in the mean total anxiety and depression scores (r = 0.17, P < 0.05).
Discussion Functional dyspepsia has often been associated with psychologi− cal distress [9]. This study, including a large sample, investigated whether endoscopy improves psychological well−being in these patients. Although a reduction in the severity of the symptoms was observed, patients with functional dyspepsia did not appear to benefit from endoscopy. This finding is noteworthy, since it has often been stated that the main reason for carrying out an
endoscopic examination is to provide the patient with reassur− ance [25, 26]. Although patients who were found to have an organic abnormal− ity at endoscopy reported a statistically significant improvement in their health−related quality of life (HRQL), the difference was so small (0.04 on a scale ranging from 0 to 1) that it has little or no clinical relevance. The improvement in symptom severity and in the mean number of symptoms in these patients was also sta− tistically significant, probably due to the treatment received after endoscopy. Nevertheless, when the mean improvement in the number of symptoms is compared between patients with an or− ganic abnormality and patients with functional dyspepsia, the difference in the improvement is only 0.5 symptoms. In addition, both groups of patients still had a considerable number of symp− toms after endoscopy, with an average of 8 or more. Using anxiety, depression, and HRQL as proxy measures for reas− surance, it was found that endoscopy does not reassure patients with upper abdominal symptoms. These results are in accord−
Van Kerkhoven LAS et al. Endoscopy and reassurance in functional dyspepsia ´ Endoscopy 2006; 38: 879 ± 885
26
40
24 22
30
20 18 20
16 14
10
12 10
0
8 R = 0.78
6 0
5
10 15 20 25 Total numbers of symptoms
30
35
Figure 1 Correlation between the total number of symptoms during the previous 4 weeks and the mean scores on the Hospital Anxiety and Depression Scale (HADS).
60 > 8 on anxiety subscale
50
> 8 on depression subscale
%
40 30 20 10 0 0–5
6–10 11–15 > 16 Total numbers of symptoms
Figure 2 The proportion of patients reporting mild to severe anxiety and depression on the Hospital Anxiety and Depression Scale.
ance with those reported recently by Spiegel et al. [27], who in− vestigated the effect of endoscopy in patients with another func− tional gastrointestinal disorder, irritable bowel syndrome, and found no independent association between a negative colonos− copy and reassurance or an improved HRQL in these patients. Several other studies have investigated the role of endoscopy in patients with dyspepsia. In the past, it has been concluded that endoscopy is a cost−effective strategy in the management of pa− tients presenting with dyspepsia [28]. More recent studies have shown that “test−and−treat” H. pylori and/or empirical PPI treat− ment are as safe and effective, or even more effective, than prompt endoscopy [29 ± 32]. The effect of an endoscopic exami− nation on psychological well−being was also investigated by Wiklund et al. [25]. They measured psychological well−being and HRQL 1 week before and 1 week after endoscopy and found that endoscopy itself led to an improvement in both measures [25]. Comparable results were found in a study in the USA in− cluding 60 patients with no organic cause for symptoms, who
0
50
100 150 200 250 Symptom severity score
300
350
Figure 3 Correlation between the symptom severity during the pre− vious 4 weeks and the total score on the Hospital Anxiety and Depres− sion Scale (HADS).
were originally recruited for a double−blind, randomized clinical study to compare omeprazole with a placebo [26]. Patients’ be− lief that they were ill and their worry about health were meas− ured 1 week before and immediately before endoscopy and im− mediately, 24 h, 1 week, 1 month, and 1 year after endoscopy, with patients being reassured that “there is nothing seriously wrong”. The results showed that immediately after the endosco− py, both the patients’ belief that they were ill and their worry about health decreased, but that the values returned to normal during the follow−up. In combination with the present results, this suggests that the initial improvement is only of brief dura− tion and disappears a month after endoscopy. The studies by both Wiklund et al. [25] and Lucock et al. [26] involve some ma− jor limitations in the study design that may have distorted the results. In addition, the time between the measurements was very short, so that the results may have been influenced by re− cognition bias. This casts doubt on the reported initial improve− ment in psychological well−being, which probably did not exist at all. Quadri and Vakil reported an improvement of six points on a scale ranging from 0 to 84 in health−related anxiety among pa− tients with high and moderate anxiety scores before endoscopy [5]. They used a disease−specific measure capable of detecting small alterations in health−related anxiety to assess the effect of open−access endoscopy. Although they reported a statistically significantly improvement, the clinical relevance of a 7 % im− provement on a disease−specific scale is debatable. The present study was designed to assess clinically relevant changes in psy− chological well−being. It is often stated that generic measures are limited because of their limited ability to detect small differen− ces. We used generic measures to assess generally experienced anxiety, depression, and HRQL and combined these data with a symptom questionnaire. In this study, this does not constitute a problem, and in fact a generic measure is preferable due to the advantage of generalizability to other populations [33]. No correlation was found between the severity of symptoms and the mean total HADS scores. This is in accordance with results
Van Kerkhoven LAS et al. Endoscopy and reassurance in functional dyspepsia ´ Endoscopy 2006; 38: 879 ± 885
Original article
4
R = 0.17
883
Competing interests: None In brief It has always been considered that a negative endoscopic exami− nation in a symptomatic patient (especially in those with dyspep− sia) has a positive effect in providing the patient with reassurance. This study argues against this assumption on the basis of patients’ Hospital Anxiety and Depression Scale scores before and after en− doscopy. Neither these parameters nor the quality−of−life score changed in patients who had no organic abnormalities. In patients who did have organic abnormalities, at least the quality of life im− proved slightly.
Original article 884
described by Jones et al. [34] in a study including 151 consecutive patients with functional dyspepsia and 90 healthy individuals, who scored their psychological distress and symptoms on vali− dated questionnaires. We would endorse the authors’ conclusion that these correlations are too weak for it to be concluded that there is a relation between the severity of symptoms and psycho− logical distress. The response rate to the first questionnaire was quite low. This was due to the fact that all of the patients referred for upper gas− trointestinal endoscopy received a questionnaire. Many patients may have considered themselves ineligible for participation in the trial because they had undergone an upper gastrointestinal endoscopy during the previous 6 months, or had an inadequate command of the Dutch language used in the questionnaire. These assumptions were confirmed by a random check on the medical records of over 10 % of the nonresponders. The actual re− sponse rate for patients undergoing their first upper gastrointes− tinal endoscopy was 64.4 %, and a response bias can therefore not be completely excluded. It is conceivable that patients with a psychiatric disorder might be either more likely or unlikely than others to return the questionnaire. However, in general, the groups of patients with and without an organic abnormality had equal scores for anxiety and depression, HRQL, and symptom severity. There is therefore no reason to assume that the re− sponse rates were different between the two groups. If any re− sponse bias is present, we would assume that it is equally dis− tributed across both groups. In summary, although there appears to be an improvement in symptom severity after endoscopy, there is no clinically relevant improvement in the psychological well−being and HRQL of pa− tients with upper gastrointestinal symptoms. In view of the inva− siveness, cost, and potential harm associated with upper gastro− intestinal endoscopy, very careful consideration should be given to whether this procedure should be carried out merely for the sake of the patient’s “peace of mind”.
Acknowledgments Funding for the present study was provided by the Stichting We− tenschappelijk Onderzoek Interne Geneeskunde (SWOIG; the Foundation for Scientific Research in Internal Medicine) at Cani− sius−Wilhelmina Hospital, Nijmegen.
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